Abstract

Recent studies have shown that many long noncoding RNAs (lncRNAs) are abnormally expressed in ovarian cancer and involved in the pathological progress of ovarian cancer. In the present study, we aimed to investigate the role of lncRNA LINC00858 and the potential mechanism in ovarian cancer. The qRT-PCR was used to measure the expression levels of LINC00858 and miR-134-5p in ovarian cancer tissue specimens and cell lines. Loss-of-function assays were performed to investigate the role of LINC00858 in ovarian cancer. MTT assay was carried out to measure cell proliferation. Transwell assays were performed to determine cell migration and invasion. Biological information analysis and luciferase report gene assay were used to verify potential downstream genes of LINC00858. The xenograft mouse model was established to analyze tumor growth in vivo. Our results showed that LINC00858 was highly expressed in human ovarian cancer tissues and cell lines. Knockdown of LINC00858 inhibited cell proliferation, migration and invasion of SKOV3 cells, and suppressed tumor growth in mouse xenograft models. Mechanistic studies revealed that LINC00858 acted as a sponge of miR-134-5p and then regulated TRIM44 expression in SKOV3 cells. Furthermore, rescue experiments illustrated that inhibition of miR-134-5p restored the inhibitory effects of LINC00858 knockdown on cell proliferation, migration and invasion. TRIM44 overexpression could counteract the inhibitory effects of miR-134-5p mimics on ovarian cancer cells. In conclusion, these findings demonstrated that LINC00858 exerted oncogenic role in ovarian cancer, which was mediated by miR-134-5p/TRIM44 axis. Thus, LINC00858 might be a therapeutic target for the treatment of ovarian cancer.

摘要

最近的研究表明，许多长链非编码RNA（lncRNA）在卵巢癌中异常表达，并参与了卵巢癌的病理进程。在本研究中，我们旨在探讨 lncRNA LINC00858 在卵巢癌中的作用及其潜在机制。qRT-PCR用于测量卵巢癌组织标本和细胞系中LINC00858和miR-134-5p的表达水平。进行功能丧失测定以研究 LINC00858 在卵巢癌中的作用。进行MTT测定以测量细胞增殖。进行 Transwell 测定以确定细胞迁移和侵袭。生物信息分析和荧光素酶报告基因检测用于验证LINC00858的潜在下游基因。建立异种移植小鼠模型分析肿瘤生长情况体内. 我们的研究结果表明，LINC00858 在人类卵巢癌组织和细胞系中高度表达。敲除 LINC00858 可抑制 SKOV3 细胞的细胞增殖、迁移和侵袭，并抑制小鼠异种移植模型中的肿瘤生长。机制研究表明，LINC00858 充当 miR-134-5p 的海绵，然后调节 SKOV3 细胞中 TRIM44 的表达。此外，救援实验表明抑制 miR-134-5p 恢复了 LINC00858 敲低对细胞增殖、迁移和侵袭的抑制作用。TRIM44 过表达可以抵消 miR-134-5p 模拟物对卵巢癌细胞的抑制作用。总之，这些发现表明 LINC00858 在卵巢癌中发挥致癌作用，这是由 miR-134-5p/TRIM44 轴介导的。因此，